So Botox Isn't Just Skin Deep

By NATASHA SINGER

Published: April 12, 2009

DR. MARK STILLMAN, the director of the Center for Headache and Pain at the Cleveland Clinic, has a treatment for people with frequent migraines: he injects Botox around the head and neck.

Dr. Andrew Blitzer, the director of the Center for Voice and Swallowing Disorders at St. Luke's-Roosevelt Hospital Center in Manhattan, has an antidote for speech impediments caused by vocal cord problems: he injects Botox into the larynx.

Dr. Fredric Brandt, a dermatologist in Manhattan and Coral Gables, Fla., has a novel procedure for oily skin and skin redness.

You guessed it: Botox.

Over the last decade, Botox has become a synonym for the eradication of wrinkles, a kind of shorthand for the entire enterprise of cosmetic medicine. But now, with the popularization of new medical uses, therapeutic applications of the drug are poised to outstrip the cosmetic treatment in both revenue and prominence.

In the hunt to discover the next blockbuster medical use for Botox, doctors have injected it experimentally into muscles and glands all over the body, making it medicine's answer to duct tape. According to recent medical journals, physicians have used it to treat chewing problems, swallowing problems, pelvic muscle spasms, drooling, hair loss, anal fissures and pain from missing limbs.

''We see it as a molecule that keeps on giving. As we understand it more, it gives us new ideas of how to use it,'' says Dr. Mitchell F. Brin, a neurologist who is the chief scientific officer for Botox at Allergan, the drug's maker.

No other therapeutic agent ''has so many demonstrated uses,'' he says.

But some health advocates worry that doctors are widely adopting novel uses for Botox before federal guidance and rigorous clinical studies have established safe and effective dosages for the new treatments.

''It's trial and error with a nerve poison,'' says Dr. Sidney M. Wolfe, the director of the health research group at Public Citizen, a consumer advocacy group. Last year, the group petitioned the Food and Drug Administration to require a warning label for injectable toxins.

BOTOX is a purified form of botulinum toxin, a nerve poison produced by the bacteria that cause botulism, a disease that paralyzes muscles and can be fatal. Injections of Botox act like minuscule poison darts that temporarily blunt chemical nerve signals to certain muscles or glands, reducing their activity.

The F.D.A. has approved Botox to treat four problems: eye muscle disorders, neck muscle disorders, excessive sweating -- and that deadly age giveaway, eyebrow furrows. But Allergan, a $14.5 billion specialty pharmaceutical company, owns or has applied for patents on more than 90 uses for the drug.

Dr. Brin of Allergan says Botox has a long safety track record -- backed by 30 years of favorable research, studies on 11,000 people worldwide and 17 million treatments in the United States since 1994.

''That safety profile has enabled us to continue to explore the product in deeper parts of the body and in more novel areas,'' Dr. Brin says. Allergan does not promote unapproved uses of the drug, he says.

Botox was developed in the 1970s by Dr. Alan Scott, an ophthalmologist in San Francisco who was searching for a cure for crossed eyes. He theorized that minute doses of a nerve poison used to weaken the muscles that pull crossed eyes inward could treat the malady, and he experimented with a variety of paralytic agents.

Then a biochemist who had isolated and purified a strain of botulinum toxin for potential military use as a biological weapon sent Dr. Scott a sample. It worked.

Dr. Scott named the new drug Oculinum. In 1989, the F.D.A. approved it to treat crossed eyes and twitching eyelids. Allergan bought Oculinum in 1991 for about $9 million, rebranding it Botox. When David E. I. Pyott became chief executive of the company in 1998, Botox had $90 million in annual sales. Last year, sales topped $1 billion.

''Nobody at Allergan understood how big a gold mine they were sitting on,'' Mr. Pyott says.

Drug companies often rely on multiple products to fill their pipelines. But at Allergan, Botox became a virtual pipeline in and of itself after the arrival of Mr. Pyott, who recognized that it was a medication that could be serially reincarnated for other applications.

Doctors, who are permitted to use approved drugs in unapproved ways as they deem appropriate, were already using Botox off-label at the time on body parts other than eye muscles. Some physicians reported that patients had unexpected side effects -- fewer headaches, for example, or smoother skin -- after they had Botox.

Mr. Pyott invested heavily in expanding in-house research and encouraged doctors to formalize their anecdotal observations with published research. He also recognized that some Americans would be willing to pay handsomely for injections that tempered wrinkles. To prove the efficacy of the drug, the company sponsored clinical trials to use Botox for cosmetic medical purposes and for other muscle disorders.

Over the last nine years, the F.D.A. has approved Botox to treat neck muscle spasms and to hinder excessive sweating. The agency also approved the same drug, under the name Botox Cosmetic, to smooth forehead wrinkles.

Last year, Botox had worldwide sales of $1.3 billion, divided about equally between cosmetic and medical uses. Among botulinum toxins, Botox has an 83 percent share of the market, Allergan said.